缬沙坦对心力衰竭家兔肌浆网钙ATP酶、蛋白激酶A及磷酸酶1α的影响

目的 探讨家兔慢性心力衰竭(心衰)时心肌肌浆网钙ATP酶(SERCA2)、心肌蛋白激酶A(PKA)和磷酸酶1α(PP1α)表达的改变及血管紧张素Ⅱ受体拮抗剂缬沙坦长期干预的意义.方法 21只家兔随机分为三组,假手术组、心衰组和缬沙坦组各7只,通过超容量负荷联合压力负荷建立家兔心衰模型,于术后7周观察左心室结构、血流动力学的变化及SERCA2、PKA、PP1α的表达.结果 与假手术组比较,心衰组左心室重量指数(LVMI)、心率、左心室舒张末压(LVEDP)显著升高(P<0.05),左心室缩短率(LVFS)及射血分数(EF)明显降低(P<0.05);与心衰组比较,缬沙坦组LVMI、心率、LVEDP显著降低(P<0.05),LVFS及EF明显升高(P<0.05);心衰组SERCA2、PKA显著低于假手术组(P<0.05),PP1α显著高于假手术组(P<0.05);缬沙坦组SERCA2、PKA显著高于心衰组(P<0.05),PP1α显著低于心衰组(P<0.05).结论 缬沙坦长期干预心衰,能够改善心脏舒缩功能,可能与其上调SERCA2、PKA表达,降低PP1α表达有关.

Effects of valsartan on sarcoplasmic reticulum calcium adenodine triphosphatase,protein kinase A and protein phosphatase 1 alpha in a rabbit model of heart failure

Objective To investigate the effects of valsartan on expressions of myocardial sarcoplasmic reticulum calcium adenodine triphosphatase(SERCA2),protein kinase A(PKA)and protein phosphatase l alpha(PP1α)in a rabbit model of heart failure.Methods Rabbits were divided into sham-operated group,heart failure group (volume overload by aortic valve destruction induced aortic insufficiency plus pressure ovedoed induced by abdominal aortic banding) and heart failure plus valsartan(20 mg·kg-1.d-1, n=6 each).Seven weeks later,echocardiography examination was performed and SERCA2.PKA.PP1α protein and mRNA expressions were detected by Western blot and RT-PCR.Results Compared with the with sham operated rabbits.LVMI and LVEDP in heart failure rabbits were significandy increased while left ventricular shorten fraction (LVFS) and ejection fraction (EF) were significantly decreased(all P<0.05),these changes could be significantly attenuated by valsartan treatment(all P<0.05).SERCA2,PKA expressions at protein and mRNA levels were significantly downregulated and PP1αexpressions significantly upregulated in heart failure rabbits than sham operated rabbits (all P<0.05) and these changes could be significantly attenuated by valsartan (all P<0.05).Conclusion Valsartan improved cardiac function in volume and pressure overload induced heart failure rabbits possibly by upregulating expressions of myocardial SERCA2.PKA and downregnlating expression of myocardial PP1α.